Kinetics of catecholamines and potassium, and heart rate during exercise testing in obese subjects. Heart rate regulation in obesity during exercise

Obesity is characterised by a marked insulin resistance which involves an abnormal regulation of K(+) uptake and metabolism. Less is known about the effect of physical exercise on K(+) kinetics

Playing around the anaerobic threshold during COVID-19 pandemic: advantages and disadvantages of adding bouts of anaerobic work to aerobic activity in physical treatment of individuals with obesity.

Obesity is a condition that generally limits work capacity and predisposes to a number of comorbidities and related diseases, the last being COVID-19 and its complications and sequelae. Physical exercise, together with diet, is a milestone in its management and rehabilitation, although there is still a debate on intensity and duration of training. Anaerobic threshold (AT) is a broad term often used either as ventilatory threshold or as lactate threshold, respectively, detected by respiratory ventilation and/or respiratory gases (VCO <sub>2</sub> and VO <sub>2</sub> ), and by blood lactic acid. This review outlines the role of AT and of the different variations of growth hormone and catecholamine, in subjects with obesity vs normal weight individuals below and beyond AT, during a progressive increase in exercise training. We present a re-evaluation of the effects of physical activity on body mass and metabolism of individuals with obesity in light of potential benefits and pitfalls during COVID-19 pandemic. Comparison of a training program at moderate-intensity exercise (< AT) with training performed at moderate intensity (< AT) plus a final bout of high-intensity (> AT) exercise at the end of the aerobic session will be discussed. Based on our data and considerations, a tailored strategy for individuals with obesity concerning the most appropriate intensity of training in the context of rehabilitation is proposed, with special regard to potential benefits of work program above AT. Adding bouts of exercise above AT may improve lactic acid and H <sup>+</sup> disposal and improve growth hormone. Long-term aerobic exercise may improve leptin reduction. In this way, the propensity of subjects with obesity to encounter a serious prognosis of COVID-19 may be counteracted and the systemic and cardiorespiratory sequelae that may ensue after COVID-19, can be overcome. Individuals with serious comorbidities associated with obesity should avoid excessive exercise intensity

ER membrane contact sites support endosomal small GTPase conversion for exosome secretion

Exosomes are endosome-derived extracellular vesicles involved in intercellular communication. They are generated as intraluminal vesicles within endosomal compartments that fuse with the plasma membrane (PM). The molecular events that generate secretory endosomes and lead to the release of exosomes are not well understood. We identified a subclass of non-proteolytic endosomes at prelysosomal stage as the compartment of origin of CD63 positive exosomes. These compartments undergo a Rab7a/Arl8b/Rab27a GTPase cascade to fuse with the PM. Dynamic endoplasmic reticulum (ER)-late endosome (LE) membrane contact sites (MCS) through ORP1L have the distinct capacity to modulate this process by affecting LE motility, maturation state, and small GTPase association. Thus, exosome secretion is a multi-step process regulated by GTPase switching and MCS, highlighting the ER as a new player in exosome-mediated intercellular communication

Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells

Accumulation of toxic amyloid oligomers is a key feature in the pathogenesis of amyloid-related diseases. Formation of mature amyloid fibrils is one defense mechanism to neutralize toxic prefibrillar oligomers. This mechanism is notably influenced by apolipoprotein E variants. Cells that produce mature amyloid fibrils to serve physiological functions must exploit specific mechanisms to avoid potential accumulation of toxic species. Pigment cells have tuned their endosomes to maximize the formation of functional amyloid from the protein PMEL. Here, we show that ApoE is associated with intraluminal vesicles (ILV) within endosomes and remain associated with ILVs when they are secreted as exosomes. ApoE functions in the ESCRT-independent sorting mechanism of PMEL onto ILVs and regulates the endosomal formation of PMEL amyloid fibrils in vitro and in vivo. This process secures the physiological formation of amyloid fibrils by exploiting ILVs as amyloid nucleating platforms

ER membrane contact sites support endosomal small GTPase conversion for exosome secretion

Exosomes are endosome-derived extracellular vesicles involved in intercellular communication. They are generated as intraluminal vesicles within endosomal compartments that fuse with the plasma membrane (PM). The molecular events that generate secretory endosomes and lead to the release of exosomes are not well understood. We identified a subclass of non-proteolytic endosomes at prelysosomal stage as the compartment of origin of CD63 positive exosomes. These compartments undergo a Rab7a/Arl8b/Rab27a GTPase cascade to fuse with the PM. Dynamic endoplasmic reticulum (ER)-late endosome (LE) membrane contact sites (MCS) through ORP1L have the distinct capacity to modulate this process by affecting LE motility, maturation state, and small GTPase association. Thus, exosome secretion is a multi-step process regulated by GTPase switching and MCS, highlighting the ER as a new player in exosome-mediated intercellular communication

ER Membrane Contact Sites support endosomal small GTPase conversion for exosome secretion

Exosomes are endosome-derived extracellular vesicles involved in intercellular communication. They are generated as intraluminal vesicles within endosomal compartments that fuse with the plasma membrane (PM). The molecular events that generate secretory endosomes and lead to the release of exosomes are not well understood. We identified a subclass of non-proteolytic endosomes at prelysosomal stage as the compartment of origin of CD63 positive exosomes. These compartments undergo a Rab7a/Arl8b/Rab27a GTPase cascade to fuse with the PM. Dynamic endoplasmic reticulum (ER)-late endosome (LE) membrane contact sites (MCS) through ORP1L have the distinct capacity to modulate this process by affecting LE motility, maturation state, and small GTPase association. Thus, exosome secretion is a multi-step process regulated by GTPase switching and MCS, highlighting the ER as a new player in exosome-mediated intercellular communication

EV-TRACK: Transparent reporting and centralizing knowledge in extracellular vesicle research

We argue that the field of extracellular vesicle (EV) biology needs more transparent reporting to facilitate interpretation and replication of experiments. To achieve this, we describe EV-TRACK, a crowdsourcing knowledgebase (http://evtrack.org) that centralizes EV biology and methodology with the goal of stimulating authors, reviewers, editors and funders to put experimental guidelines into practice